The long range objective of this study is the elucidation of the mechanisms of differential regulation of hemoglobin synthesis in erythroid cells. The factors responsible for the control of production of the structurally different human hemoglobin types are not well understood. This control could be exerted at any of the several stages of the process of protein synthesis. However, translational control now seems less likely and messenger RNA stability and/or transcriptional control may be important. Understanding of these control processes would be of great importance in clarifying the defects in hemoglobin synthesis in several disease states including the hemoglobinopathies, sickle cell anemia, and thalassemia. The immature erythroid cells of bone marrow and the peripheral reticulocytes constitute a readily accessible model system for the in vitro study of protein synthesis. Such cells will be obtained from normal subjects and patients with hemoglobinopathies and thalassemia and mRNA isolated for in vitro testing of stability.